Bazedoxifene (1-[4-(2-azepan-1-yl-ethoxy)-benzyl]-2-(4-hydroxy-phenyl)-3-methyl-1H-indol-5-ol; or bazedoxifene free base), having the chemical formula shown below:
belongs to the class of drugs typically referred to as selective estrogen receptor modulators (SERMs). Consistent with its classification, bazedoxifene and its salts demonstrate affinity for estrogen receptors (ER) but show tissue selective estrogenic effects. For example, bazedoxifene acetate demonstrates little or no stimulation of uterine response in preclinical models of uterine stimulation. Conversely, bazedoxifene acetate demonstrates an estrogen agonist-like effect in preventing bone loss and reducing cholesterol in an ovariectomized rat model of osteopenia. In an MCF-7 cell line (human breast cancer cell line), bazedoxifene acetate behaves as an estrogen antagonist. These data demonstrate that bazedoxifene is estrogenic on bone and cardiovascular lipid parameters and antiestrogenic on uterine and mammary tissue and thus has the potential for treating a number of different disease or disease-like states wherein the estrogen receptor is involved.
U.S. Pat. Nos. 5,998,402 and 6,479,535 report the preparation of bazedoxifene and salts thereof. The synthetic preparation of bazedoxifene and its salts has also appeared in the general literature. See, for example, Miller et al., J. Med. Chem., 2001, 44, 1654-1657.
Further description of the drug's biological activity has appeared in the general literature as well (e.g. Miller, et al. Drugs of the Future, 2002, 27(2), 117-121).
Because drug formulations showing, for example, improved stability, solubility, and bioavailability are consistently sought, there is an ongoing need for new forms of existing drug molecules. The ascorbic acid salt of bazedoxifene and compositions containing the same described herein helps meet these and other needs.